Nonsteroidal anti-inflammatory drugs(NSAIDs)

NSAIDs:  Nonsteroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, but also referred to as nonsteroidal anti-inflammatory agents/analgesics (NSAIAs) ornonsteroidal Anti-inflammatory medicines (NSAIMs), are drugs with analgesic and antipyretic (fever-reducing) effects and which have, in higher doses, anti-inflammatory effects.

The term "nonsteroidal" is used to distinguish these drugs from steroids, which, among a broad range of other effects, have a similar eicosanoid-depressing, anti-inflammatory action. As analgesics, NSAIDs are unusual in that they are non-narcotic.

CLASSIFICATION OF NSAIDs

NONSELECTIVE NSAIDS:

Nonselective NSAIDs inhibit the enzymes found in the stomach, blood platelets, and blood vessels (COX-1) as well as the enzymes found at sites of inflammation (COX-2) to a similar degree. Nonselective NSAIDs include drugs such as aspirin, ibuprofen, naproxen and diclofenac.

SELECTIVE NSAIDS:

Selective NSAIDs (also called COX-2 inhibitors) inhibit the COX enzyme found at sites of inflammation (COX-2) more than the type of enzyme normally found in the stomach, blood platelets, and blood vessels (COX-1). Celecoxib is a selective NSAID.

(or)

CLASSIFICATION OF NSAIDs:

1) COX-1 SELECTIVE INHIBITORS
- acetylsalicylic acid at low dosage

2) NONSELECTIVE COX INHIBITORS
- acetylsalicylic acid at high dosage
- diclofenac
- ibuprofen
- ketoprofen
- flurbiprofen
- indomethacin
- piroxicam
- naproxen

3) MORE COX-2 SELECTIVE INHIBITORS
- nimesulid
- etodolak
- meloxicam
- nabumeton

4) COX-2 SELECTIVE INHIBITORS
- celecoxib
- etorcoxib
- valdecoxib

NSAIDS   MOA :

Nonsteroidal Antiinflammatory Drugs MOA:

How do the nonsteroidals work? They work very high up in the chain when you have cell trauma. The lipase is liberated and the nonsteroidals work there. Nonsteroidals block cyclooxygenase (COX)-1 and -2 and prevent the pathway of arachidonic acid, cyclic endoperoxidase, and thromboxane, prostaglandin, and prostacyclin production. The problem is the body exists in a constant balance. We have alpha receptors and beta receptors to keep our blood pressure in check and to keep an adequate amount of vasoconstriction and dilatation; it's a balance. When we give a blocker of one, we override on the other. That's what happens here. We block our prostaglandins and now we have a preponderance of leukotrienes.

 

ANTI-INFLAMMATORY EFFECTS OF NSAIDs

This effect of NSAIDs is due to the inhibition of the enzyme COX, which converts arachidonic acid to prostaglandins, TXA2 and prostacyclin.

Acetylsalicylic acid irreversibly inactivates COX-1 and COX-2 by acetylation of a specific serine resideu.

Other NSAIDs reversibly inhibit COX-1 and COX-2

Additional anti-inflammatory mechanism may include:

- interference with the potentiative action of other mediators of inflammation – bradykinin, histamine, serotonin
- modulation of T-cell function
- stabilization of lysosomal membranes
- inhibition of chemotaxis

ANALGESIC EFFECT OF NSAIDs

This effect of NSAIDs is thought to be related to the peripheral inhibition of prostaglandin production, but it may also be due to the inhibition of pain stimuli at a subcortical site.
NDAIDs prevent the potentiating action of prostaglandins on endogenous mediators
of peripheral nerve stimulation ( e.g. bradykinin )

ANTIPYRETIC EFFECT OF NSAIDs

This effect is believed to be related to inhibition of the interleukin-1 and interleukin-6 induced production of prostaglandins in the hypothalmus and the „ resetting „ of the termoregulatory system, leading to vasodilation and increased heat loss


CLINICAL USES O NSAIDs
1) analgesia
2) inflammation
3) antipyresis
4) antiplateled effect
5) cancer preventive agents 

ADVERSE EFFECTS OF NSAIDs:

1) gastrointestinal effects: abdominal pain, gastric and duodenal ulcer, diarrhea, pancreatis
gastrointestinal hemorrhage, hepatotoxicity
2) renal effects
- disturbances of renal function with water and sodium retention
3) inhibition of platelet aggregation
4) central symptoms: headache, decreased hearing, tinnitus, dizziness, confusion, dpression
5) allergic reactions: asthma, rashes, photosensitivity
 

side effects of NSAIDs:

NSAIDs are associated with several side effects. The frequency of side effects varies among NSAIDs. The most common side effects are nausea, vomiting, diarrhea, constipation, decreased appetite, rash, dizziness, headache, and drowsiness. NSAIDs may also cause fluid retention, leading to edema. The most serious side effects are kidney failure, liver failure, ulcers and prolonged bleeding after an injury or surgery..

PHARMACODYNAMIC INTERACTION NSAIDs WITH OTHER DRUGS

NSAIDs + hypotensive drugs ( β-blockers, ACE-inhhibitors, diuretics ) = ↓ hypotensive effect
NSAIDs + ehanol = ↑risk of bleeding from gastrointestinal tract
NSAIDs + ticlopidine or clopidogrel = ↑risk of bleeding
NSAIDs + lithium = ↑lithium toxicity
NSAIDs + cylosporine or ACE-inhibitors or takrolimus= ↑nephrotoxicity of drugs
NSAIDs + fluoroquinolons = ↑ toxic action of fluoroquinolons on CNS
NSAIDs +oral antidiabetic drugs =↑ risk of hypoglycemia
NSAIDs + cumarines = ↑risk of bleeding from gastrointestinal tract

PHARMACOKINETIC INTERACTION NSAIDs WITH OTHER DRUGS

NSAIDs + oral antidiabetic drugs = ↑ risk of hypoglycemia
NSAIDs + cumarines =↑risk of bleeding
NSAIDs + corticosteroids = ↑risk gastropathy and bleeding from gastrointestinal tract
NSAIDs + aminogycosides = ↑ ototoxicity and nephrotoxicity of aminogycosides
NSAIDs + fenytoine or valproinic acid = ↑action of fenytoine or valproinic acid
NSAIDs + metotrexat or digoxin = ↑action and ↑ toxicity metotrexat or digoxin
NSAIDs + tricycles antidepressive drugs neuroleptics or antiarrhytmic drugs or
selective serotonin reuptake inhibitors ( SSRI ) = ↑ action of drugs